Abstract
BackgroundThe human gut microbiota has been identified as a potentially important factor influencing the development of COVID-19. It is believed that the disease primarily affects the organism through inflammatory pathways. With the aim of improving early diagnosis and targeted therapy, it is crucial to identify the specific gut microbiota associated with COVID-19 and to gain a deeper understanding of the underlying processes. The present study sought to investigate the potential causal relationship between the gut microbiota and COVID-19, and to determine the extent to which inflammatory proteins act as mediators in this relationship.MethodsBidirectional mendelian randomization (MR) and Two-step mediated MR analyses were applied to examine causative associations among 196 gut microbiota, 91 inflammatory proteins and COVID-19. The main analytical method used in the MR was the random effects inverse variance weighted (IVW) method. This was complemented by the Bayesian weighted Mendelian randomization (BWMR) method, which was utilized to test the hypothesis of MR. In order for the results to be deemed reliable, statistical significance was required for both methods. Validation was then carried out using an external dataset, and further meta-analyses were conducted to authenticate that the association was reliable.ResultsResults of our research indicated that seven gut microbiota were actively associated to the COVID-19 risk. Five inflammatory proteins were associated with COVID-19 risk, of which three were positively and two were negatively identified with COVID-19. Further validation was carried out using sensitivity analyses. Mediated MR results revealed that CCL2 was a possible mediator of causality of family Bifidobacteriaceae and order Bifidobacteriales with COVID-19, mediating at a ratio of 12.73%.ConclusionSuggesting a genetic causation between specific gut microbiota and COVID-19, our present research emphasizes the underlying mediating role of CCL2, an inflammatory factor, and contributes to a deeper understanding of the mechanism of action underlying COVID-19.